Wednesday, December 13, 2017

Possible Cures for Type-1 in the News (December)

Here are some "bits and pieces" updates for December.

Update on Dr. Faustman's Phase-II Trial of BCG

Dr. Faustman's lab has published their Fall 2017 newsletter, which you can read here:
This newsletter includes more information on her research, especially from the 3rd International BCG conference, The BCG Working Group, and the 2nd edition of the BCG and Autoimmunity book she edited.

There are three pieces of new news there:
  1. The phase-II trial was fully enrolled in Summer of 2017. This is important because we now  know when the trial will end.  Since this is a five year study, they should finish collecting data in Summer of 2022 and publish before Summer of 2023. 
  2. They have given BCG to the three untreated patients from their phase-I trial, so they will have data from six people to report in the future. 
  3. The lab is going to be recruiting for more studies in the future, so would like to hear from anyone who is interested in participating.  No details on future trials were provided.
Another piece of news is that Dr. Faustman is branching out, and trying to apply BCG treatment to Fibromyalgia.  This research is being done in collaboration with EpicGenetics, and they hope to start the trial in early 2018.  If anything applicable to the type-1 world comes up in this research, I'll report it.  Since Fibromyalgia is not generally considered an autoimmune disease, I'm not sure how much "cross pollination" of results there will be.  You can read more about it here:

DILfrequency Trial Completed

There is a lot of research ongoing on IL-2 which is part of the immune system.  About 18 months ago, I summarized all this research here:
with an update here:

One of those clinical trials was called "DILfrequency" and that trial has finished, and the results published.  The purpose of that trial was to develop the best dosing method of IL-2 which could then be used in future trials.  ("Best" in this case, meant a stable and known change in the immune system, which the researchers wanted.)  It was successful in terms of telling the researchers what they wanted to know to prepare for future clinical studies.

There are several IL-2 research projects either ongoing or planned to start (including by this group), so I think we'll get a stronger signal in the next few years.

Journal Article:
Clinical Trial Record:

Joshua Levy
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Thursday, November 30, 2017

IMCY-0098 Starts a Phase-I Clinical Trial

I always enjoy blogging about a clinical trial for a new treatment, done by a new company, which hopes to cure type-1 diabetes. As I understand it, Imcyse, the company doing this research, has a method for creating peptides (small pieces of a protein) which will generate a type of immune cell that is able to destroy the immune cells of the body responsible for the disease. If this works, they can specifically target the cells that are causing autoimmune diseases. The company is going after Type-1 Diabetes (first), Multiple Sclerosis (second), and several other diseases after that. IMCY-0098 is the code name for their peptide targeting T1D.

IMCY-0098 Starts a Phase-I Clinical Trial

This study started in Aug 2017 and they hope to finish in Dec 2018.  They will enroll a total of 40 adult honeymooners (within 6 months of diagnosis) divided up into three groups. In addition to their regular insulin treatments, each group will get a total of 4 injections over 2 months (just below the skin, like an insulin injection).  One group will get low dose injections, one group medium dose injections, and the third group will get high dose injections; and each group will contain some controls who will get a placebo.  Patients will be followed for 6 months.  The researchers will track safety issues, effectiveness (C-peptide, A1c, etc.), and changes in the immune system.

They are currently recruiting in Belgium, Denmark, Cardiff and Oxford, and plan to start soon in France, Germany and additional location in the UK.  The list is long, and you can see the exact locations in their clinical trial record:


The company's web site includes this page:
which discusses how they are developing their treatments.  Unfortunately, it is too technical for me to understand.  But for readers with a background in immunology, this page might be valuable.

Joshua Levy 
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Sunday, November 19, 2017

Possible Cures for Type-1 in the News (November)

Merck Cancels "Smart Insulin" (MK-2640) After Unsuccessful Phase-I Trial

This is the news everyone hoped we would not get.  After completing a phase-I trial of "Smart Insulin" (also known as MK-2640), Merck has decided not to move forward with it.  They have not published the results, but have published this: "MK-2640 was discontinued due to lack of efficacy".

News report:


This was the first (and so far only) glucose responsive insulin to be tested in humans.  However, there are several "smart insulins" being tested in animals, not to mention "smart artificial cells" and "smart membrane" based technologies, all aimed at automatically regulating the amount of insulin in the blood stream.  I expect some of these to enter human trials in the next few years.  So "smart insulin" may yet be a trail blazer, even if it itself was unsuccessful.

If results from this study are ever published, I'll blog on them here.  However, there is nothing forcing Merck to publish these results if they don't want to.

Phase-II T-Rex Trial Update

Caladrius Biosciences recently announced that they had enrolled the 70th patient (out of 111) in their clinical trial of CLBS03 for T1D.  So it has taken them roughly 18 months to recruit 2/3 of the patients they need.  If they can keep up that pace, they will finish recruiting in the third quarter of 2018, and finish collecting data in the third quarter of 2019, and publish in 2020.

Previous Blogging:

A quick summary of this treatment is as follows: remove one specific type of T regulator cell (called "CD4(+)CD25(+)CD127(lo)") from a person with type-1 diabetes.  Grow them out so you have about 500 times more, and then put them back in the same person.  Since regulatory T cells naturally regulate the body's immune system, and the patient now has more of them, the hope is that they will prevent the autoimmune attack which causes type-1 diabetes.

They are recruiting patients in about 15 locations all over the US, so read the clinical trial registry to get a complete list and some contact information.

News Report:
Clinical Trial Registry:

SIMPONI (Golimumab) Starts A Phase-I Trial In Pre-Symptomatics

Golimumab (sold as Simponi) is an immune system modulator, which has been approved in the United States and many other countries for treatment of several autoimmune diseases, so testing it on type-1 diabetes makes a lot of sense.  This is the second trial underway for this drug.  (The other one is called T1GER, and is for honeymooners.)  Simponi has already been approved to treat rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and ankylosing spondylitis.

This study is recruiting people who have two autoimmune antibodies (but no other symptoms of type-1 diabetes). They are recruiting 30 kids (aged 6-21), and will follow them for 17 months. Each kid will get 26 weekly injections.  Half the patients will get Simponi and the other half will get a placebo.  They hope to finish this study in mid 2021.

This study is current recruiting in Linkoping University Hospital, Linkoping, Sweden, SE 58185.
Study contact: 844-434-4210
They hope to start recruiting at other locations in Sweden and Finland soon.

The unusual thing about this trial is that they will not measure any effectiveness data at all.  The only data gathered will be safety and side effect data.  No C-peptide data, no A1c, or insulin usage.  That's very unusual for a type-1 diabetes study.  In my experience, even the phase-I studies gather some effectiveness data.

Clinical Trial Record:
Previous Clinical Trial Record:

Joshua Levy
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Sunday, November 5, 2017

Results From Phase-I Clinical Trial of Proinsulin Peptide Vaccine in Honeymooners (MonoPepT1De)

For over 10 years there has been a research group at Cardiff University (UK) working on creating vaccine-like treatments to cure or prevent type-1 diabetes, and this blog posting covers their recent results.

As background: one of the autoantibodies that is associated with type-1 diabetes targets insulin molecules [d1]. Therefore, there is a theory that giving people with T1D a protein fragment from insulin might prevent or delay the onset of type-1 diabetes.  It would train the body not to produce this autoantibody. The process is vaguely similar to giving small amounts of peanut proteins to people with peanut allergies [d2].  These researchers are using a peptide (a small part of a protein) from proinsulin, which is a precursor of insulin.

Results From Phase-I Clinical Trial of Proinsulin Peptide Vaccine in Honeymooners

This trial involved 27 people divided into three groups.  One group got a placebo and was a control group, the other two groups got the Proinsulin Peptide injections for 6 months.  One group got the peptide every 2 weeks, the other every 4 weeks.  The people were adult, honeymoon diabetics (within 100 days of first insulin injection).  They will be followed for 3 years, although this publication only covers the first year after treatment.

The untreated group went through a normal honeymoon period, where over time they gradually generated less and less of their own insulin, and had to inject more and more.  However, the treated people (on average) held steady in their ability to generate their own insulin, and did not lose their ability to generate insulin for the time covered. So this meant that the treated group did better than the untreated group over time, and the difference was statistically significant.  Also, there were no safety issues.

JDRF funded this trial specifically, and this whole line of research, in general.

News Coverage:
Full Paper:
Clinical Trial Record:


I think there are three important points for this research:

First, these results are good enough to spur a phase-II trial, and the Cardiff researchers have already made it clear they hope to run a phase-II trial starting in 2018.  Two of the authors of this paper are consultants to UCB Pharma to help design that trial.  So that is good.

These results join a growing number of treatments with what I call "medium good" results in honeymooners.  "Medium good" means that the treated group did not get worse, but did not improve either.  This is in comparison to the untreated group which did get worse.  (During the honeymoon phase, people with type-1 diabetes get worse: they gradually lose the ability to generate insulin.  They go from generating a little insulin, to generating none.)  I think there are about half a dozen treatments which have phase-I or phase-II? results of this type.  So it's better than nothing, but because none of these treatments have moved forward to even better results, I'm not not particularly excited about them.  I'm still hoping for better results in future trials.

These "medium good" results may become even more valuable in the future, if they can be applied to people in the earliest stages of type-1 diabetes, when they have two autoantibodies, yet are not showing any other symptoms.  I'm hopeful that preserving insulin generation at that level could delay or prevent needing injections completely.

Second, this same research group is working on another clinical trial closely related to this one, but it has not gotten as far along the development path:  (This is an 8 person clinical trial without a control group.)

Finally, this same research group is working on a similar treatment, but based on many peptides, rather than just one.  That trial is called MultiPepT1De:
They completed recruiting on 3 July 2017, so should finish gathering data about the end of 2017.


[d1] Autoantibodies are the malfunctioning antibodies which cause the immune system to attack beta cells. There are five autoantibodies associated with type-1 diabetes, and there may be more that we haven't discovered yet. The five we know about are:
* micro insulin autoantibodies (mIAA or just IAA)
* islet-cell antibodies (ICA)
* glutamic acid decarboxylase (GAD) antibodies
* islet antigen-2 (IA-2) antibodies
* zinc-transporter 8 (ZnT8) autoantibodies

[d2] It is important to realize that type-1 diabetes is NOT a conventional allergy to insulin. It is similar to allergies in that it is the body's immune system overreacting to something that it should not react to, but other than that, is quite different. Allergies involve the immune system overproducing histamines. These histamines attempt to get physical irritants, like pollen, out of your body. You can counter this histamine reaction by taking antihistamines. Type-1 diabetes involves the immune system overproducing malfunctioning killer T-cells (or perhaps under producing regulatory T-cells). These malfunctioning killer T-cells mistakenly kill beta cells, thinking they are foreign cells (ie. living creatures like viruses, that have invaded the body). So the mechanism is different (histamines vs. T-cells), and the mistaken target is different (physical things, like pollen or wheat vs. living organisms, like viruses).

Joshua Levy 
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Friday, October 6, 2017

JDRF Funding for a Cure 2017

In the US, we are in the "Walking Season" when JDRF asks us to walk to raise money for a cure. So I'd like to do my part, by reminding you all of how important JDRF is to the human trials of potential cures for type-1 diabetes, which I track.

Let me give you the punch line up front: 63% of the treatments currently in human trials have been funded by JDRF. (And the number is 81% for the later phase trials.) This is a strong impact; one that any non-profit should be proud of. This summary does not include Artificial Pancreas research or stem cell growth trials, because there are so many of those that it would be hard to include them all.

Below is a list of all the potential cures, grouped by phase of trial that they are currently in, and separated into potential cures that JDRF has funded, and those that JDRF has never funded.

This list is a list of treatments, and many of these are being tested in more than one clinical trial.  For example, the "ATG and autotransplant" treatment is actually running three trials, but since they are all testing the same treatment, it is only one item in the list. The list below uses the following marks to show the nature of the treatments:
    (Established) One or more trials are open to people who have had type-1 diabetes for over a year.
    (Presymptomatics) One more more trials are open to people who have 2 or more autoantibodies, but have not yet started showing symptoms of type-1 diabetes.
    (Prevention) This treatment is aimed at preventing type-1 diabetes, not curing it.

Also remember that I give an organization credit for funding a treatment if they funded it at any point in development; I don't limit it to the current trial. For example, JDRF is not funding the current trials for AAT, but they did fund earlier research into it, which helped it grow into human trials. I also include indirect funding of various kinds. For example, the JDRF funds nPOD,  ITN, and several other organizations, so I include research done by these other groups as well.

Starting Last Year: Phase-II? Trials
Starting last year, I divided Phase-II trials into two groups.  Phase-II trials are "classic" phase-II trials; they are done after a successful Phase-I trial in type-1 diabetes.  What I call Phase-II? trials are done with treatments which are known safe, so they don't need Phase-I trials, but have never been tested on type-1 diabetes before.  These Phase-II? trials might be Phase-II from the point of view of safety, but they are Phase-I in terms of effectiveness, so I'm putting them in their own category.

Cures in Phase-III Human Trials
Summary: currently there is only one treatment in a phase-III clinical trial, and that is aimed at prevention.  It is funded by JDRF.  While I see the benefit of prevention, this is the sixth year in a row there have been no phase-III trials aimed at curing existing type-1 diabetes, and it's not a good thing. Even worse, I don't see a phase-III study starting even next year.  Some people might be discouraged by that, but for me, it's a reason to donate.  Money is the thing that is going to move the Phase-II studies listed below into Phase-III studies, and the Phase-I studies to Phase-II, create more Phase-I studies, and so on.
  • Oral Insulin (Preventative) 
Cures in Phase-II Human Trials
Summary: there are 22 trials in phase-II, and 17 of them have been funded by JDRF, while 5 have not. Here are the treatments that have been funded by JDRF:
  • AAT (Alpha-1 Antitrypsin) by Grifols Therapeutics and also Kamada 
  • ATG and GCSF by Haller at University of Florida (Established) 
  • Abatacept by Orban at Joslin Diabetes Center 
  • Abatacept by Skyler at University of Miami (Prevention) 
  • Aldesleukin (Proleukin) at Addenbrooke’s Hospital, Cambridge, UK 
  • Diabecell by Living Cell Technologies (Established) 
  • Diamyd, Ibuprofen ("Advil"), and Vitamin D by Ludvigsson at Linköping University
  • Diamyd, Etanercep, and Vitamin D  by Ludvigsson at Linköping University
  • Diamyd and Vitamin D by Larsson at Lund University (Prevention)
  • Gleevec by Gitelman at UCSF 
  • Gluten Free Diet: Three Studies  (Preventative)
  • Polyclonal Tregs by both Trzonkowski and Gitelman  
  • Stem Cell Educator by Zhao (Established) 
  • Teplizumab (AbATE study team) 
  • Teplizumab by Herold/Skyler/Rafkin (Prevention)
  • Tocilizumab by Greenbaum/Buckner at Benaroya Research Institute 
  • Umbilical Cord Blood Infusion by Haller at University of Florida 
  • Ustekinumab by University of British Columbia
  • Verapamil by Shalev/Ovalle at University of Alabama at Birmingham
Not funded by JDRF:
  • ATG and autotransplant by Burt, and also Snarski, and also Li 
  • BCG by Faustman at MGH (Established) 
  • Dual Stem Cell by Tan at Fuzhou General Hospital 
  • Stem Cells of Arabia (Established)
  • Vitamin D by Stephens at Nationwide Children's Hospital (Prevention)
Cures in Phase-II? Human Trials
Summary: there are 8 trials in phase-II, and 2 of them has been funded by JDRF, while 7 have not. Here are the treatments that have been funded by JDRF:
  • Rituximab by Pescovitz at Indiana University
  • Intranasal Insulin by Harrison at Melbourne Health (Prevention)
Not funded by JDRF:
  • Albiglutide by GlaxoSmithKline
  • Golimumab by Janssen
  • Ladarixin by  Emanuele Bosi of Dompé Farmaceutici
  • Liraglutid (Presymptomatics)
  • NNC0114-0006 and Liraglutide by Novo-Norsk
  • Rapamycin Vildagliptin Combo by IRCCS (Established)
Cures in Phase-I Human Trials
Summary: there are 24 trials in phase-I, and 15 of them are funded by JDRF, while 9 are not. Here is the list funded by JDRF:
  • Alefacept by TrialNet 
  • ßAir by Beta-O2's at Uppsala University Hospital in Sweden (Established) 
  • TOL-3021 by Bayhill Therapeutics (Established) 
  • CGSF by Haller at University of Florida 
  • Trucco at Children’s Hospital of Pitt / Dendritic Cells (DV-0100) by DiaVacs (Established) 
  • Exsulin and Ustekinumab by Rosenberg at Jewish General Hospital, Canada (Established) 
  • IBC-VS01 by Orban at Joslin Diabetes Center  
  • Metformin by Littleford at The University of Exeter (Prevention)
  • MultiPepT1De (Multi Peptide Vaccine) by Powrie at King’s College London
  • Nasal insulin by Harrison at Melbourne Health (Prevention)
  • Smart Insulin (MK-2640) by Merck (Established) 
  • Tauroursodeoxycholic Acid (TUDCA) by Goland at Columbia University
  • Polyclonal Tregs by both Trzonkowski and Gitelman 
  • Pro insulin peptide by Dayan at Cardiff University 
  • VC-01 by Viacyte (Established)
Not funded by JDRF:
  • CGSF and autotransplant by Esmatjes at Hospital Clinic of Barcelona (Established) 
  • Encapsulated Islets at University clinical Hospital Saint-Luc (Established) 
  • Gluten Free Diet by Carlsson at Lund University
  • Mesenchymal Stromal Cell by Carlsson at Uppsala University
  • Microvesicles (MVs) and Exosomes by Nassar at Sahel Teaching Hospital 
  • Monolayer Cellular Device (Established) 
  • Rilonacept by White at University of Texas 
  • Substance P by Vanilloid Genetics at Hospital for Sick Children Toronto (Established)
  • The Sydney Project, Encapsulated Stem Cells (Established) 
    Summary of all Trials
    55 in total
    35 funded by JDRF
    So 63% of the human trials currently underway are funded (either directly or indirectly) by JDRF. Everyone who donates to JDRF should be proud of this huge impact; and everyone who works for JDRF or volunteers for it, should be doubly proud.

    Just Looking at Trials on Established Type-1 Diabetics
    17 of these treatments (31%) are being tested on established type-1 diabetics.
    Of these, 8 are funded by JDRF
    So 47% of the trials recruiting established type-1 diabetics are funded by JDRF.

    Compared to Last Year
    In 2016 there were 42 treatments in clinical trials, in 2017 there are 55 (growth of 31%)
    In 2016 there were no treatments in Phase-III trials, in 2017 there is one.
    In 2016 there were 22 treatments in Phase-II and Phase-II? trials, in 2017 there are 30 (growth of 36%).
    In 2016 there were 20 treatments in Phase-I trials, in 2017 there are 24 (growth of 20%).

    A Little Discussion

    Although the growth of 31% looks really good, I'm a little worried that that high growth number is because of a mistake on my part.  In previous years, I would review the research and remove everything that had failed or was going nowhere for too long.  However, this year, I was hit by some extra work at my real job, and so did not have time to check the older research to see if it was still active.  My guess is that some of the research still listed here really should be removed, and I'll do that over the next few months.  Still, I do think there was growth this year, just not 31% growth.

    How I Count Trials for This Comparison
    • I give an organization credit for funding a cure if it funded that cure at any point in it's development cycle. 
    • I mark the start of a research trial when the researchers start recruiting patients (and if there is any uncertainty, when the first patient is dosed). Some researchers talk about starting a trial when they submit the paper work, which is usually months earlier. 
    • If there are different clinical trials aimed at proving effectiveness as a cure and as a preventative, or effectiveness in honeymooners and established diabetics, then those are counted separately. 
    • For trials which use combinations of two or more different treatments, I give funding credit, if the organization in the past funded any component of a combination treatment, or if they are funding the current combined treatment. Also, I list experiments separately if they use at least one different drug. 
    • The ITN (Immune Tolerance Network) has JDRF as a major funder, so I count ITN as indirect JDRF funding. 
    • I have made no attempt to find out how much funding different organizations gave to different research. This would be next to impossible for long research programs, anyway. 
    • Funding of research is not my primary interest, so I don't spend a lot of time tracking down details in this area. I might be wrong on details. 
    • I use the term "US Gov" for all the different branches and organizations within the United States of America's federal government (so includes NIDDK, NIAID, NICHD, etc.) 
    • I don't work for the US Gov, JDRF, or any of the other organizations discussed here. I have a more complete non-conflict of interest statement on my web site. 
    Some Specific Notes:
    • Oral Insulin: This trial was a phase-III trial, meaning that it was large and designed to provide enough information so that if, if successful, the treatment could be widely used. However, as it turned out, only part was successful, and that part was phase-II sized, so I don't think we will see widespread use based on this trial alone. You can think of this as a phase-III trial with phase-II results.
    • Serova's Cell Pouch and DRI's BioHub: These two clinical trials are both testing one piece of infrastructure which might be used later in a cure. They are testing a part of a potential cure. However, in both cases, the clinical trials being run now require immunosuppression for the rest of the patient's life, so I'm not counting them as testing a cure.
    • Substance P at Hospital for Sick Children Toronto: This trial is avoiding the honeymoon period by testing for insulin production.  Patients must inject more than 1/2 unit/kg to be accepted, therefore they will accept recently diagnosed people, if they are injecting enough insulin to be passed the honeymoon.  I'm counting this as "Established".
    This is an update and extension to blog postings that I've made for the previous seven years:
    Finally, please remember that my blog (and therefore this posting) covers research aimed at curing or preventing type-1 diabetes that is currently being tested in humans. There is a lot more research going on, not covered here.

    Please think of this posting as being my personal "thank you" note to all the JDRF staff, volunteers, and everyone who donates money to research a cure for type-1 diabetes:
    Thank You!
    Finally, if you see any mistakes or oversights in this posting, please tell me! There is a lot of information packed into this small posting, and I've made mistakes in the past.  As in previous years, I'll be at the Santa Clara (California) JDRF One Walk.  Come by and say "hi", or strike up a conversation about research.  I love to talk about research!

    Joshua Levy
    publicjoshualevy at gmail dot com 
    All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

    Sunday, October 1, 2017

    Important Update For Stem Cells Arabia

    If you are interested in potential cures for type-1 diabetes, then I urge you to read this report from the JDCA about Stem Cells Arabia:
    (Note that as a Fellow of the JDCA, I did contribute to their report.)

    Stem Cells Arabia is in the middle of a clinical trial were they combine two stem cell procedures as a possible cure for type-1 diabetes.  However, the real excitement is fueled by the results of a very small pilot study they did previously.  The results from the pilot study were presented at a conference, but not published in a journal.  But those results are very strong: all four treated patients went months without needing to inject insulin and never needed anti-rejection drugs.  If you find that exciting (and I certainly do), then you'll want to read the JDCA report which contains more details, and you'll be looking forward to the results of their larger trial, which is expected to complete in early 2019.

    Joshua Levy
    publicjoshualevy at gmail dot com
    All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

    Monday, September 18, 2017

    Possible Cures for Type-1 in the News (September)

    Catching Up With NNC0114­-0006 (Anti IL-21)

    Back in 2015 Novo-Norsk started a clinical trial into a combo treatment of NNC0114-0006 and Liraglutide (which is more commonly known as Victoza).  I ignored this trial, because I thought that NNC0114-0006 was a new form of insulin, and they were testing a treatment for type-1 diabetes. However, I have since found out that NNC0114-0006 targets IL-21 and that Liraglutide may stimulate beta cell growth.  Therefore, this combination could have the effect of stopping the autoimmune attack while at the same time regrowing beta cells, and that would be a path to a cure.

    Liraglutide is approved for use in type-2 diabetes and works by increasing insulin production. Recently, experiments in mice have suggested that it works (at least partly) by helping the body grow more beta cells, and preventing the death of beta cells:

    NNC0114-0006 is an anti IL-21 treatment.  IL-21 is a chemical that the immune system uses for communication, and several experiments have suggested that too much IL-21 is important to creating type-1 diabetes:
    (and there are many more such studies.)

    So combining these two treatments provides a possible path to a cure.

    The Current Study

    The study that started in 2015 is a phase-II? trial (the question mark means that it is a phase-II trial, but there has never been a phase-I trial for this combination of treatments).  The basic study design is four groups: one group gets both treatments, one group gets two placebos, one group gets NNC0114-0006 and placebo, and one group gets Liraglutide and a placebo.  So they have all their bases covered. The study is large: 304 people recruited from 100+ sites all over the US and Europe.

    The clinical trial record says that this study is recruiting patients.  However, when I look at the list of locations, every one is marked "Active, not recruiting", "Completed", or "Suspended", so I'm very hopeful that they have recruited all the patients that they need.  That is important, because they expect to collect data for 80 weeks.  Their target completion date is April 2019.

    This is actually the fifth study of NNC0114­-0006.  You can see the list here:
    The four previous studies were smaller (between 10 and 65 people), and were done on other autoimmune diseases: Rheumatoid Arthritis, Crohn's Disease, and Systemic Lupus Erythematosus.

    Clinical Trial Registry:
    Other Study ID Numbers: NN9828-4150
    2014-001215-39 ( EudraCT Number )
    U1111-1154-7172 ( Other Identifier: WHO )
    REec-2015-1768 ( Registry Identifier: Spanish registry )

    Metreleptin Fails A Phase-I Trial

    Back in the 2008-2010 timeframe there was some hope that Leptin would cure type-1 diabetes, and a clinical trial was started in 2010.  Then in 2015 the trial was canceled by one of the sponsors.  Finally, now in 2017 the results have been published, and the conclusions are:
    Metreleptin is safe but may not be efficacious in improving glycemic control in patients with T1DM, although it reduces body weight and daily insulin dose modestly.
    You can read my previous blogging here:
    The abstract is here:
    Clinical Trial Record:

    Interesting Treatment for Multiple Sclerosis

    I usually do not blog on cures or treatments for other diseases.  However, MS, type-1 diabetes and several other diseases are all from the same family of "autoimmune diseases".  They are all caused by the body's immune system attacking a different organ or internal system.  So in theory, research into curing one of these diseases might help cure the others.

    So with that in mind, I thought this study was interesting:
    Multiple Sclerosis Therapy NKTR-358 Begins Phase 1 Clinical Trial:

    Basically, this company has a treatment which causes a person to generate more Treg cells.  Since Treg cells regulate the immune system, having more of them might prevent the immune system from attacking the wrong cells.  In type-1 diabetes, we have several research programs aimed at increasing Treg counts, but usually by growing more Tregs outside the body, and then infusing them into the body (T-Rex, Stem Cell Educator, and Stem Cells of Arabia are all working on similar ideas). NKTR-358 is a treatment which (they hope) will cause the body to generate more Treg cells, itself.

    Also, NKTR-358 works at least partially, by targeting the IL-2 receptor in the immune system, and this receptor is also an active target of research in type-1:
    (and the IL-2 targeted by NKTR-358 is different than the IL-21 targeted by NNC0114-0006 above.)

    Company Information:
    Some animal data:

    Joshua Levy 
    publicjoshualevy at gmail dot com 
    All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.